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'Gateway' gene discovered for brain cancer
February 15, 2007Researchers have discovered that the same genetic regulator that triggers growth of stem cells during brain development also plays a central role in the development of the lethal brain cancer malignant glioma. In experiments on mice with such gliomas, they showed that knocking out the function of a particular regulatory protein, Olig2, almost completely eliminated tumor formation.
The researchers said their findings suggest that targeting Olig2 could offer a potential avenue for treatment that would kill tumor cells without affecting normal tissue.
Dana-Farber Cancer Institute investigators Charles Stiles and David Rowitch and their colleagues reported their findings in the February 15, 2007 issue of the journal Neuron, published by Cell Press.
Olig2 is a "transcription factor"—a protein that regulates the activity of genes. Prior studies had indicated that it plays a central role in enabling neural stem cells to replicate during embryonic brain development. Also, studies have suggested that brain tumors might arise from aberrant neural stem cells or the neural progenitor cells to which they give rise.
Analyzing tissue from human gliomas, Stiles, Rowitch, and their colleagues discovered that Olig2 is activated in the stem and progenitor cells found in the tumors. In a mouse model of malignant glioma, they found that knocking out Olig2 function prevented tumor formation in 91 percent of the animals.
Their analysis of the role of Olig2 in both tumor cells and normal neural stem cells revealed that it plays a key role in enabling cell growth. Specifically, they found that Olig2 represses the gene for a cell-replication "brake" called p21, which normally inhibits cell growth. Thus, they concluded that Olig2 is a "unifying feature of normal cell cells and malignant glioma" and a "gateway" gene for brain tumor development.
"Lineage-restricted pathways that regulate brain tumor behavior may represent more specific therapeutic targets with little potential to affect off-target cell types," commented the researchers.
"Brain tumors remain a major cause of cancer-related death despite advances in surgery, imaging, and conventional treatment modalities," they wrote. "This emphasizes the need to develop novel medical strategies based on a comprehensive understanding of the biological mechanisms underlying gliomagenesis."
They wrote that "our findings identify this core transcriptional regulator as an important candidate for antitumor therapeutics." While transcription factors are not generally considered useful targets for anti-cancer drugs, there are multiple ways that Olig2 could be inhibited, as well as ways to target other components of the regulatory pathway by which it exerts its influence on tumor growth, wrote the researchers.
Cell Press
Olig2 is a "transcription factor"—a protein that regulates the activity of genes. Prior studies had indicated that it plays a central role in enabling neural stem cells to replicate during embryonic brain development. Also, studies have suggested that brain tumors might arise from aberrant neural stem cells or the neural progenitor cells to which they give rise.
Analyzing tissue from human gliomas, Stiles, Rowitch, and their colleagues discovered that Olig2 is activated in the stem and progenitor cells found in the tumors. In a mouse model of malignant glioma, they found that knocking out Olig2 function prevented tumor formation in 91 percent of the animals.
Their analysis of the role of Olig2 in both tumor cells and normal neural stem cells revealed that it plays a key role in enabling cell growth. Specifically, they found that Olig2 represses the gene for a cell-replication "brake" called p21, which normally inhibits cell growth. Thus, they concluded that Olig2 is a "unifying feature of normal cell cells and malignant glioma" and a "gateway" gene for brain tumor development.
"Lineage-restricted pathways that regulate brain tumor behavior may represent more specific therapeutic targets with little potential to affect off-target cell types," commented the researchers.
"Brain tumors remain a major cause of cancer-related death despite advances in surgery, imaging, and conventional treatment modalities," they wrote. "This emphasizes the need to develop novel medical strategies based on a comprehensive understanding of the biological mechanisms underlying gliomagenesis."
They wrote that "our findings identify this core transcriptional regulator as an important candidate for antitumor therapeutics." While transcription factors are not generally considered useful targets for anti-cancer drugs, there are multiple ways that Olig2 could be inhibited, as well as ways to target other components of the regulatory pathway by which it exerts its influence on tumor growth, wrote the researchers.
Cell Press
Brain Cancer Current Events and Brain Cancer News RSSCancer metabolism discovery uncovers new role of IDH1 gene mutation in brain cancer
Agios Pharmaceuticals today announced that its scientists have established, for the first time, that the mutated IDH1 gene has a novel enzyme activity consistent with a cancer-causing gene, or oncogene.
Magnetic nanoparticles to simultaneously diagnose, monitor and treat
Whether it's magnetic nanoparticles (mNPs) giving an army of 'therapeutically armed' white blood cells direction to invade a deadly tumour's territory, or the use of mNPs to target specific nerve channels and induce nerve-led behaviour (such as the life-dependant thumping of our hearts), mNPs have come a long way in the past decade.
Angiochem crosses BBB, shows safety, efficacy in phase 1/2 brain cancer studies
Angiochem, Inc. a clinical-stage biotechnology company developing drugs that are uniquely capable of crossing the blood-brain barrier to treat brain diseases, announced today that its lead drug candidate, ANG1005, has demonstrated a favorable safety and efficacy profile in more than 100 patients with brain cancer from two separate Phase 1 /2 clinical studies in patients with progressive gliomas, including recurrent glioblastoma, and in patients with progressive brain metastases.
Toward a nanomedicine for brain cancer
In an advance toward better treatments for the most serious form of brain cancer, scientists in Illinois are reporting development of the first nanoparticles that seek out and destroy brain cancer cells without damaging nearby healthy cells.
UM scientists pinpoint critical molecule to celiac disease, possibly other autoimmune disorders
It was nine years ago that University of Maryland School of Medicine researchers discovered that a mysterious human protein called zonulin played a critical role in celiac disease and other autoimmune disorders, such as multiple sclerosis and diabetes.
Experts warn over health check brain scans
A new study has voiced concern about the growing market for brain screening tests, which people can buy as part of a general health MOT.
Avastin dramatically improves response, survival in deadly recurrrent glioblastomas
The targeted therapy Avastin, alone and in combination with the chemotherapy drug CPT-11, significantly increased response rates, progression-free survival times and survival rates in patients with a deadly form of brain cancer that had recurred.
Computational Process Zeroes in on Top Genetic Cancer Suspects
Johns Hopkins engineers have devised innovative computer software that can sift through hundreds of genetic mutations and highlight the DNA changes that are most likely to promote cancer.
NIH study reveals new genetic culprit in deadly skin cancer
Drawing on the power of DNA sequencing, National Institutes of Health researchers have identified a new group of genetic mutations involved in the deadliest form of skin cancer, melanoma.
NIH researchers identify key factor that stimulates brain cancer cells to spread
Researchers funded by the National Institutes of Health have found that the activity of a protein in brain cells helps stimulate the spread of an aggressive brain cancer called glioblastoma multiforme (GBM).
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